Sympathetic preganglionic neurons in the intermediolateral columns of the spinal cord are recognized as important integrating centers for central regulation of blood pressure and other autonomic functions. Together with their regulatory pathways, these neurons may also be involved in the etiology of essential hypertension and other cardiovascular disorders. The specific aims of this proposal are to determine the functions, physiology, and pharmacology of sympathetic preganglionic neurons and the monoaminergic, neuropeptide, and other central pathways by which their activity is controlled by the central nervous system. Specifically, this project is designed (1) to test further the hypothesis that the excitability of sympathetic preganglionic neurons is regulated in part by catecholamine pathways which act by altering the intraneuronal levels of cyclic AMP, (2) to characterize the respective functions, distribution, and pharmacology of two populations of descending excitatory pathways to sympathetic preganglionic neurons and the respective roles of monoamines in producing both short- and long-term changes in synaptic transmission in these pathways, and (3) to determine the effects and the possible functional roles of certain neuropeptides that are found in high concentrations in the neuropil of sympathetic preganglionic neurons. Each phase will be investigated by 2 or 3 approaches using standard electrophysiological technics which include recording evoked activity from preganglionic rami alone, during systemic drug administration, or during micropressure injection of putative transmitters or drugs into identified segmental pools of preganglionic neurons; and recording single-unit activity both alone and during micropressure application of putative transmitters or drugs. Data acquisi-and analysis will rely on standard signal averaging and unit-recording technics. The experiments are designed to provide results that are mutually complementary and discriminatory with regard to the respective neurophysiology, neurochemistry, and neuropharmacology of monoaminergic, neuropeptide, and other pathways to sympathetic preganglionic neurons. Basic information about regulatory mechanisms operating at this site may have broader applicability and will contribute to further understanding of central regulatory mechanisms that control blood pressure and may be involved in the etiology and treatment of essential hypertension and other autonomic dysfunctions.